Characterization of immune anomalies caused by the <i>ptpn6</i>Ala457Thr mutation associated with a specific form of pulmonary emphysema
Bibliographic record
Abstract
Abstract A new mutation (PTPN6 Ala455Thr) was recently discovered in a family in which many members developed a severe, early and panacinar form of pulmonary emphysema. The mutation was found to be located in the PTPN6 gene, encoding a tyrosine phosphatase known as SHP-1. SHP-1 regulates immunological signaling pathways, such as those involved in B cells maturation and activation. To characterize the impact of the ptpn6 Ala457Thr mutation in a mouse model on subpopulations of B lymphocytes and on their response to immunization. Proportions of B1a et B2 cells were analyzed in the lungs and spleens of 4-month old mice carrying the ptpn6 Ala457Thr mutation by flow cytometry. Serum immunoglobulin levels were assessed. Another group of mice were immunized with a T cells-independent antigen (NP-Ficoll, 50ug i.p.). Plasma was collected at different timepoints after immunization and NP-specific antibodies were measured by ELISA (IgG1, IgG3, IgM and IgA). Mice carrying the ptpn6 Ala457Thr mutation mice had a higher proportion of B1a cells and a lower proportion of B2 cells in the spleen and in the lungs. Total IgG and IgM levels in the serum were higher in ptpn6 Ala457Thr mice compared to wild-type animals. Following immunization with NP-Ficoll, ptpn6 Ala457Thr mice displayed levels of NP-specific IgG3 and IgM similar to those observed in wild-type mice. However, ptpn6 Ala457Thr mice had lower levels of NP-specific IgG1 antibodies compared to the wild-type group. SHP-1 seems to be important for B cell differentiation and functions, as the mutation led to significant changes in B cell subpopulations. It seems that SHP-1 plays an important role in the immune response to immunization. The full scope of the immunological effects of this mutation requires further study.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".